AB0449 ASSOCIATION OF OPG, OPN AND OCN PROTEINS WITH THE RISK OF RHEUMATOID ARTHRITIS
Authors: J. Hu, C. LI, Z. Zhang, J. Qiao, S. X. Zhang, C. Wang, X. LI
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Rheumatoid arthritis (RA) is a chronic inflammatory disease characterised by joint swelling, joint compression and synovial joint destruction, where inflammation and bone destruction can lead to significant functional impairment. Recently, several studies have reported the identification of new biomarkers of RA, such as osteoprotegerin (OPG), osteocalcin (OCN) and osteopontin (OPN)<sup>[1]</sup>, all three of which play a significant role in regulating bone metabolism and influencing osteoclast synthesis and secretion. Although OPG, OCN and OPN are strongly correlated with RA, it is not clear whether there is a causal relationship between them. <h3>Objectives</h3> The aim of this study was to assess whether OPG, OPN and OCN are causally related to the risk of RA in a Two-Sample Mendelian randomisation(TSMR). <h3>Methods</h3> The genetic instrumental variables (IVs) for OPG, OPN and OCN exposure from a large genome-wide association study (GWAS) meta-analysis including 21,758, 1322 and 3301 participants, respectively. The GWAS data for RA were selected from an independent RA GWAS analysis that included 29,880 RA cases of European ancestry and 73,758 controls.Significant (P &lt; 5 × 10-6) and independent (r2&lt; 0.001) SNP in genome-wide association studies were selected as IVs for performing MR analyses. The causal relationship between OPN、OPG、OCN and RA risk was assessed by TSMR analysis using inverse variance weighting (IVW) methods as the primary analysis, supplemented by weighted median, MR-Egger. MR-Egger regression, Leave-one-out analysis and Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used to detect and correct for the effects of horizontal multi-effects<sup>[2]</sup>. <h3>Results</h3> The Eighteen,seven and nine SNPs were selected as IVs for OPN, OPG and OCN respectively. The results of theIVW method (OPN:OR = 1.0191, 95% CI: 0.9800-1.0597, p = 0.3440; OPG: OR = 1.0396, 95% CI: 0.9327- 1.1588, p = 0.4827;OCN: OR = 1.077, 95% CI: 0.990- 1.077, p = 0.812) showed that there was no strong evidence of a relationship between the production of OPN, OPG and OCN in people of European ancestry and RA risk. Further sensitivity analyses verified the robustness of the above associations, with MR-Egger regressions showing no evidence of pleiotropy (OPN:p = 0.8703; OPG:p = 0.7043;OCN:p = 0.6356) and heterogeneity analyses showing no heterogeneity (OPN:p = 0.7880; OPG:p = 0.2451;OCN:p =0.5651). The leave-one-out method analysis indicated that genetically determined PN, OPG and OCN were not driven by any single SNP in association with RA risk. <h3>Conclusion</h3> We did not find any evidence of a causal relationship between OPN, OPG,OCN and RA risk. Further research is needed to elucidate the potential mechanisms underlying the role of OPN, OPG and OCN in the development of RA. <h3>References</h3> [1]Liu LN, Mao YM, Zhao CN, et al. Circulating Levels of Osteoprotegerin, Osteocalcin and Osteopontin in Patients with Rheumatoid Arthritis: A Systematic Review and Meta-Analysis. Immunol Invest 2019; 48: 107-120. [2]Davey Smith G and Hemani G. Mendelian randomization: genetic anchors for causal inference in epidemiological studies. Hum Mol Genet 2014; 23: R89-98. <h3>Acknowledgements:</h3> NIL. <h3>Disclosure of Interests</h3> None Declared.